CA2024694A1 - Acyloxymethyl esters of bisphosphonic acids as bone resorption inhibitors - Google Patents

Acyloxymethyl esters of bisphosphonic acids as bone resorption inhibitors

Info

Publication number
CA2024694A1
CA2024694A1 CA2024694A CA2024694A CA2024694A1 CA 2024694 A1 CA2024694 A1 CA 2024694A1 CA 2024694 A CA2024694 A CA 2024694A CA 2024694 A CA2024694 A CA 2024694A CA 2024694 A1 CA2024694 A1 CA 2024694A1
Authority
CA
Canada
Prior art keywords
bisphosphonic acids
bone resorption
acyloxymethyl esters
resorption inhibitors
treatment
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA2024694A
Other languages
French (fr)
Other versions
CA2024694C (en
Inventor
Walfred S. Saari
Paul S. Anderson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck and Co Inc
Original Assignee
Merck and Co Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck and Co Inc filed Critical Merck and Co Inc
Publication of CA2024694A1 publication Critical patent/CA2024694A1/en
Application granted granted Critical
Publication of CA2024694C publication Critical patent/CA2024694C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids RP(=O)(OH)2; Thiophosphonic acids, i.e. RP(=X)(XH)2 (X = S, Se)
    • C07F9/40—Esters thereof
    • C07F9/4071—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4075—Esters with hydroxyalkyl compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids RP(=O)(OH)2; Thiophosphonic acids, i.e. RP(=X)(XH)2 (X = S, Se)
    • C07F9/40—Esters thereof
    • C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4025—Esters of poly(thio)phosphonic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/58—Pyridine rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/59—Hydrogenated pyridine rings

Abstract

The invention relates to acyloxymethyl esters of bisphosphonic acids, halo-bisphosphonic acids and hydroxy-bisphosphonic acids which exhibit oral bioavailability and are useful in the treatment of disturbances involving calcium or phosphate metabolism, in particular, the treatment and prevention of diseases involving bone resorption, especially osteoporosis, Paget's disease, malignant hypercalcemia, and metastatic bone disease.
CA002024694A 1989-09-06 1990-09-05 Acyloxymethyl esters of bisphosphonic acids as bone resorption inhibitors Expired - Fee Related CA2024694C (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US40341189A 1989-09-06 1989-09-06
US403,411 1989-09-06

Publications (2)

Publication Number Publication Date
CA2024694A1 true CA2024694A1 (en) 1991-03-07
CA2024694C CA2024694C (en) 2000-10-17

Family

ID=23595658

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002024694A Expired - Fee Related CA2024694C (en) 1989-09-06 1990-09-05 Acyloxymethyl esters of bisphosphonic acids as bone resorption inhibitors

Country Status (5)

Country Link
EP (1) EP0416689B1 (en)
JP (1) JPH07119230B2 (en)
CA (1) CA2024694C (en)
DE (1) DE69023844T2 (en)
LV (1) LV11473B (en)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2114946T3 (en) * 1991-09-05 1998-06-16 Toray Industries DERIVATIVE OF METHANODIPHOSPHONIC ACID, ITS PRODUCTION AND MEDICINAL USE.
US5283057A (en) * 1992-04-24 1994-02-01 The Procter & Gamble Company Risedronate in oral compositions
HUT69699A (en) * 1992-05-29 1995-09-28 Procter & Gamble Pharma Sulfur-containing phosphonate compounds for treating abnormal calcium and phosphate metabolism
NZ272608A (en) 1994-07-22 2000-05-26 Lilly Co Eli Inhibiting bone loss by administering a bisphosphonate and a second compound selected from various compounds, including 2-phenyl-3-aroylbenzothienes; bisphosphonate combination salts
SE9703691D0 (en) * 1997-10-10 1997-10-10 Astra Ab Pharmaceutical compositions
FI104901B (en) * 1997-10-20 2000-04-28 Leiras Oy New methylene bisphosphonic acid derivatives
US6818787B2 (en) 2001-06-11 2004-11-16 Xenoport, Inc. Prodrugs of GABA analogs, compositions and uses thereof
FR2837490B1 (en) * 2002-03-21 2009-04-17 Univ Paris 13 NOVEL DERIVATIVES OF BISPHOSPHONATES, THEIR PREPARATIONS AND USES
CA2451881A1 (en) * 2001-07-16 2003-01-30 Universite Paris 13 Novel bisphosphonate derivatives, their preparation methods and uses
US6927036B2 (en) 2002-02-19 2005-08-09 Xero Port, Inc. Methods for synthesis of prodrugs from 1-acyl-alkyl derivatives and compositions thereof
US7662987B2 (en) 2003-07-15 2010-02-16 Xenoport, Inc. Methods for synthesis of acyloxyalkyl compounds
KR101140559B1 (en) 2003-08-20 2012-07-05 제노포트 인코포레이티드 Acyloxyalkyl carbamate prodrugs, methods of synthesis and use
EP1716115B1 (en) 2003-12-30 2013-02-27 XenoPort, Inc. Synthesis of acyloxyalkyl carbamate prodrugs and intermediates thereof
JP4938771B2 (en) 2005-06-20 2012-05-23 ゼノポート，インコーポレーテッド Acyloxyalkyl carbamate prodrugs of tranexamic acid, methods of synthesis, and uses
US7531572B2 (en) 2006-07-28 2009-05-12 Xenoport, Inc. Acyloxyalkyl carbamate prodrugs of α-amino acids, methods of synthesis and use

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2534391C2 (en) * 1975-08-01 1983-01-13 Henkel KGaA, 4000 Düsseldorf 1-Hydroxy-3-aminoalkane-1,1-diphosphonic acids
DE2745083C2 (en) * 1977-10-07 1985-05-02 Henkel KGaA, 4000 Düsseldorf Hydroxydiphosphonic acids and processes for their preparation
FR2531088B1 (en) * 1982-07-29 1987-08-28 Sanofi Sa ANTI-INFLAMMATORY PRODUCTS DERIVED FROM METHYLENEDIPHOSPHONIC ACID AND THEIR PREPARATION METHOD
GB8419489D0 (en) * 1984-07-31 1984-09-05 Leo Pharm Prod Ltd Chemical compounds
GB8530603D0 (en) * 1985-12-12 1986-01-22 Leo Pharm Prod Ltd Chemical compounds
DE3623397A1 (en) * 1986-07-11 1988-01-14 Boehringer Mannheim Gmbh NEW DIPHOSPHONIC ACID DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS

Also Published As

Publication number Publication date
EP0416689A3 (en) 1991-06-26
LV11473A (en) 1996-08-20
LV11473B (en) 1996-12-20
JPH03106893A (en) 1991-05-07
JPH07119230B2 (en) 1995-12-20
DE69023844T2 (en) 1996-06-20
EP0416689B1 (en) 1995-11-29
DE69023844D1 (en) 1996-01-11
CA2024694C (en) 2000-10-17
EP0416689A2 (en) 1991-03-13

Similar Documents

Publication Publication Date Title
CA2149052A1 (en) Dry mix formulation for bisphosphonic acids
CA2024694A1 (en) Acyloxymethyl esters of bisphosphonic acids as bone resorption inhibitors
CA2188567A1 (en) Wet granulation formulation for bisphosphonic acids
PT1914237E (en) Phosphonate ester antiviral compounds
PT939748E (en) Gypsum-boards having increased resistance to permanent deformation
CA2018477A1 (en) Process for preparing 4-amino-1-hydroxybutylidene-1, 1-bisphosphonic, acid monosodium salt trihydrate
AU1876788A (en) Methylene phosphonoalkylphosphinates, pharmaceutical compositions , and methods for treating abnormal calcium and phosphate metabolism
CA2035179A1 (en) Pharmaceutical compositions containing insoluble salts of bisphosphonic acids
EP0341961A3 (en) Polymalonic acids as boneaffinity agents
HUP9802219A3 (en) Processes for the preparation of n-phosphonomethylglycine from n-phosphonomethyliminodiacetic acid
GB8902740D0 (en) Process for the preparation of triaryl phosphate
HU901602D0 (en) Continuous process for the production of solid calcium phosphates from raw phosphate without the addition of phosphoric acid and lime
LTIP1742A (en) Process for the preparation of phosphoric or thiophosphoric acid ethylenimides
EP0417558A3 (en) S-haloalkyl(di)(tri)(thio)phosphoric(phosphonic)acid(amide) esters
EP0723968A3 (en) Process for the preparation of thiophosphoric acid 0,0'-diesters and their salts as well as their preparation
CA2192456A1 (en) Pyridylbisphosphonates for use as a therapeutical agent
HUP0004653A3 (en) The use of bisphosphonates for producing medicaments use ful for inhibiting bone resorption
FR2620118B1 (en) PROCESS FOR THE MANUFACTURE OF PHOSPHATE FERTILIZERS AND PRODUCTS OBTAINED
IE873052L (en) Calcium phosphate scale inhibition

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed